GABAergic neurons that pioneer hippocampal area CA1 of the mouse: Morphologic features and multiple fates

Abstract

Dramatic changes occur in the expression of glutamic acid decarboxylase (GAD67) immunoreactivity in mouse hippocampus during postnatal development. Most striking is the presence of a dense population of immunopositive cells in stratum radiatum and stratum oriens in area CA1 during the first postnatal week. Between days 5 and 10, these cells disappear and the GAD67 immunoreactivity begins to resemble that of adulthood. These neurons are considered pioneer cells, and studies were undertaken to determine their fate. Between days 5 and 50, area CA1 doubles in size; however, the loss of cells expressing GAD67 mRNA cannot be explained solely by dilution resulting from hippocampal growth. In stratum radiatum, cell loss is particularly dramatic. Although between days 5 and 15, many cells seem to migrate from stratum radiatum to its border with stratum lacunosum-moleculare, both fate maps of pioneer cells labeled with bromodeoxyuridine (BrdU) on embryonic day 13 (E13) and in situ DNA end-labeling studies suggest that some cells die by means of programmed cell death. However, not all pioneer cells die, because many cells labeled with BrdU on E13 are present in adulthood and express markers for and have anatomic features of hippocampal interneurons. In conclusion, events that underlie the age-dependent disappearance of gamma-aminobutyric acid (GABA) -ergic pioneer cells are complex and cannot be completely explained by dilution in an expanding neuropile. Although some GABAergic pioneer cells likely undergo programmed cell death during the first postnatal weeks, others relocate within hippocampal laminae and terminally differentiate into the interneurons of adulthood.